Species

cd45 antigens

Summary

Summary: High-molecular weight glycoproteins uniquely expressed on the surface of all leukocytes and their hemopoietic progenitors. The CD45 family consists of multiple members that are all products of a single gene. CD45 expression is necessary for signaling through the T-cell receptor.

..However, the refractory state of CD4(+)CD25(+) T cells was partially reversible by the addition of IL-2 or IL-4. These data demonstrate that human blood contains a resident T cell population with potent regulatory properties...

..2001). These findings suggest that myo-endothelial progenitors reside in the interstitial spaces of mammalian skeletal muscles, and that they can potentially contribute to postnatal skeletal muscle growth...

Isolation and direct characterization of resident microglial cells from the normal and inflamed central nervous system

..Uncoupling environmental and intrinsic defects in chimeric mice, we demonstrated that CD45 regulates progenitor movement and retention by influencing both the hematopoietic and nonhematopoietic compartments...

Origin and distribution of bone marrow-derived cells in the central nervous system in a mouse model of amyotrophic lateral sclerosis

..Thus, we demonstrate that the microgliosis present in spinal cord tissue of mSOD mice is primarily due to an expansion of resident microglia and not to the recruitment of microglial precursors from the circulation...

The role of CD45 and CD45-associated molecules in T cell activation

J G AltinDivision of Biochemistry and Molecular Biology, School of Life Sciences, Faculty of Science, Australian National University, Canberra, AustraliaImmunol Cell Biol 75:430-45. 1997

..This review aims to summarize recent findings on the role of CD45 and CD45-associated molecules in T cell activation, and to highlight issues that seem relevant to ongoing research in this area...

..Achieving a thorough understanding of the biological reasons for the existence and tight regulation of CD45 isoform expression in immune cells remains one of the outstanding challenges in the CD45 research field...

..MDM-derived HIV contained 26 of 37 proteins previously found in exosomes, consistent with the idea that HIV uses the late endosome/multivesicular body pathway during virion budding from macrophages...

..The higher ability of 129Sv mice to produce IFN-alpha in vivo is related to a higher number of pDC, but also to a higher ability of pDC from 129Sv mice to produce IFN-alpha in vitro in response to viral stimulation...

..We conclude that CD45 is not required at any stage during the generation of mature peripheral B cells, however its loss reveals a previously unrecognized role for CD45 in the regulation of certain subpopulations of B cells...

CD4+ CD8+ thymocytes are preferentially induced to die following CD45 cross-linking, through a novel apoptotic pathway

..The brains showed no or a negligible vascular expression of MRP8 and MRP14. Information about the local microglia density in the normal human brain can serve as a reference for the evaluation of pathological microglial responses...

..Taken together, the loss of HIV-specific CD4+ T cells is associated with a combination of an infection of CCR5+ CD127+ memory CD4+ T cells, possibly in GALT, and a high expression of the inhibitory receptor CTLA-4...

Neural stem cells in the subventricular zone are a source of astrocytes and oligodendrocytes, but not microglia

..Our results stress that the langerin(+) DC network is more complex than originally thought and have implications for the development of transcutaneous vaccines and the improvement of humanized mouse models...

..However, this technique has not been applied to the study of cerebral ischemia inflammation. The aim of this study was to establish a flow cytometric method to measure inflammatory cells in ischemic brain...

Developing lymph nodes collect CD4+CD3- LTbeta+ cells that can differentiate to APC, NK cells, and follicular cells but not T or B cells

..Since the necessity of lymphotoxin in lymphoid organ development has been shown, we propose that the novel subset of CD4+CD3-LTbeta+ fetal cells is instrumental in the development of lymphoid tissue architecture...

..Thus, CD45 is moving rapidly back into the spotlight as a drug target and central regulator involved in differentiation of multiple hematopoietic cell lineages, autoimmunity and antiviral immunity...

Mutations in the tyrosine phosphatase CD45 gene in a child with severe combined immunodeficiency disease

Melissa A Cosenza-NashatDepartment of Science, BMCC, City University of New York, New York, NY, USABrain Pathol 16:256-65. 2006

..RO was low in control microglia, but increased in HIVE. RO was also localized to macrophages and CD8+ T cells. Targeting CD45 in vivo with isoform-specific antibodies remains a therapeutic option for neuroinflammatory diseases...

..Perturbation of this function may contribute to autoimmunity, immunodeficiency, and malignancy. Moreover, recent advances suggest that modulation of CD45 function can have therapeutic benefit in many disease states...

CD45 isoforms expression on CD4+ and CD8+ T cells throughout life, from newborns to centenarians: implications for T cell memory

..Our data therefore suggest that mobilization of resident CD45(+) stem cells is an important factor in regeneration after injury and highlight the Wnt pathway as a potential therapeutic target for degenerative neuromuscular disease...

Evidence that HIV budding in primary macrophages occurs through the exosome release pathway

..These results strongly support the Trojan exosome hypothesis and its prediction that retroviral budding represents exploitation of a pre-existing cellular pathway of intercellular vesicle trafficking...

..It is suggested that this stretch of amino acids may be part of the catalytic center of PTPases...

Productive HIV-2 infection in the brain is restricted to macrophages/microglia

Andreas MörnerDepartment of Immunology and Molecular Pathology, University College London, UKAIDS 17:1451-5. 2003

..The aim of this study was to detect productive HIV-2 infection in the brain and investigate whether HIV-2 has an expanded tropism for brain cells in vivo, in comparison with HIV-1, which productively infects macrophages/microglia...

..We conclude that CD45 is regulated differentially in myeloid and lymphoid cells and that sequences critical to direct myeloid expression include a PU.1 binding site upstream of the P1b transcriptional initiation site...

Inhibition of granulocyte-macrophage colony-stimulating factor signaling and microglial proliferation by anti-CD45RO: role of Hck tyrosine kinase and phosphatidylinositol 3-kinase/Akt

..An L-CA+ revertant was obtained and the ability to proliferate in response to antigen and cross-linked CD3 was restored. These data indicate that L-CA is required for T cells to enter into cell cycle in response to antigen...

TcR-alpha/beta(+) CD4(-)CD8(-) T cells in humans with the autoimmune lymphoproliferative syndrome express a novel CD45 isoform that is analogous to murine B220 and represents a marker of altered O-glycan biosynthesis

..We find no evidence of a B220- memory B cell population that is not explicable by antigen-capturing cells, and warn that care must be taken when using antigen-specificity or surface IgG as an indicator of B cell memory...

Negative regulation of CD45 by differential homodimerization of the alternatively spliced isoforms

..Unexpectedly, the CD45RB low-density cells prevent the CD45RBhigh expressing cells from causing rejection. These data suggest that the response to foreign tissue can be controlled in the same way as the response to self-tissue...

Regulation of the p70zap tyrosine protein kinase in T cells by the CD45 phosphotyrosine phosphatase

..Our observations demonstrate the utility of CD45 immunoaffinity-based approaches for producing highly purified retrovirus preparations for applications that would benefit from the use of virus that is essentially free of microvesicles...

..Absence of MyD88 in CD4(+)CD45Rb(high) cells results in defective T cell function, especially Th17 differentiation. These results suggest a role for TLR signaling by T cells in the development of inflammatory bowel disease...

Pax7 is necessary and sufficient for the myogenic specification of CD45+:Sca1+ stem cells from injured muscle

..It appeared that dogs with high percentages of CD45+ suffered from long-lasting CNS disease with seizures. In future studies, the reason and consequences for upregulated CD45 in long-lasting CNS diseases has to be further evaluated...

..Taken together, these results strongly suggest a role for the extracellular and/or the transmembrane portion of CD45 in apoptosis signaling, which contrasts with the previously reported functions for CD45 in T lymphocytes...

A point mutation in PTPRC is associated with the development of multiple sclerosis

..Collectively, peripheral blood homeostasis of CD4+T cells is disturbed in R-WG with the persistent expansion of non-regulatory CD4+TEM cells. These cells might be involved in relapse and may constitute a target for therapy...

..The experiments outlined utilize state of the art technologies in molecular biology and extracellular matrix biochemistry to probe the pathogenesis of glomerulosclerosis, a critical issue at the forefront of nephrology...

..We anticipate that these interventions will ultimately enhance the prognosis for patients with relapsed lymphoma by increasing the response and survival rates, while simultaneously minimizing toxicities. ..

..Nickel as PI has the experience, expertise and the proven ability to design, implement and enroll patients with CPPS in clinical studies and will be a valuable partner in the proposed CPCRN and UCPPSCG. ..

..The identification of chemokines that promote allergic asthma is an important step in the future development of therapeutics to target specific molecules within the airways. [unreadable] [unreadable] [unreadable]..

..Overall, the primary aim of the study is to heighten understanding of the mechanisms underlying the role of men in nonmarital childbearing, as well as the early involvement of men with their children. ..

..This information, together with a specific YopH inhibitor that works in the same T cell activation model, will represent valuable progress towards the goal of designing a drug to combat plague mortality. ..

..The proposed studies will generate synaptic mechanisms for fast glutamatergic transmission as well as 5-HT regulation in the spinal cord. This information will be important for understanding central pain transmission and modulation. ..

..Identification of an adult human stem cell population with the ability to generate differentiated cell types would offers extraordinary therapeutic potential for repair of the lungs (and other organs) following injury. ..

..These studies should provide important insights into the links between immune regulation, autoimmunity, and lymphoid malignancies as well as improve our understanding of the mechanisms governing immune surveillance. ..

..This information could be applied to not only stimulate neural regeneration to treat sight-threatening diseases of the retina, but also to control gliosis that may be detrimental to the pathogenesis of retinal disorders. ..

..In toto, the studies proposed in this grant will increase the knowledge about pathogenesis of AIDS associated thrombocytopenia and may lead to development of new strategies for its treatment of prevention. (End of Abstract) ..

..4) Determine whether the generation of a diverse TCR repertoire contains populations of high-avidity CTL that come to dominate the population of CTL during chronic infection and mediate control of HIV- 1 replication. ..